Year: 2014
Type: article
Abstract: BACKGROUND: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies. METHODS: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity. RESULTS: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)). CONCLUSIONS: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.
Authors: Linda Broer, Aron S. Buchman, Joris Deelen, Daniel S. Evans, Jessica D. Faul, Kathryn L. Lunetta, Paola Sebastiani, Jennifer A. Smith, Albert V. Smith, Toshiko Tanaka, Lei Yu, Alice M. Arnold, Thor Aspelund, Emelia J. Benjamin, Philip L. De Jager, Gudny Eirkisdottir, Denis A. Evans, Melissa E. Garcia, Albert Hofman, Robert C. Kaplan, Sharon L. R. Kardia, Douglas P. Kiel, Ben A. Oostra, Eric S. Orwoll, Neeta Parimi, Bruce M. Psaty, Fernando Rivadeneira, Jerome I. Rotter, Sudha Seshadri, Andrew Singleton, Henning Tiemeier, André G. Uitterlinden, Wei Zhao, Stefania Bandinelli, David A. Bennett, Luigi Ferrucci, Vilmundur Gudnason, Tamara B. Harris, David Karasik, Lenore J. Launer, Thomas T. Perls, P. Eline Slagboom, Gregory J. Tranah, David R. Weir, Anne B. Newman, Cornelia M. van Duijn, Joanne M. Murabito
Institutions: Leiden University Medical Center, Erasmus MC, Netherlands Consortium for Healthy Ageing, Rush University Medical Center, California Pacific Medical Center, University of Michigan, Institute for Social Research, Boston University, Framingham Heart Study, University of Iceland, Icelandic Heart Association, National Institute on Aging, University of Washington, Broad Institute, Brigham and Women's Hospital, Harvard University, National Institutes of Health, Albert Einstein College of Medicine, Beth Israel Deaconess Medical Center, Hebrew SeniorLife, Oregon Health & Science University, Group Health Cooperative, Kaiser Permanente Washington Health Research Institute, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, Erasmus MC - Sophia Children’s Hospital, Azienda Sanitaria di Firenze, Bar-Ilan University, Boston Medical Center, University of California, San Francisco, University of Pittsburgh
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Illinois Department of Public Health, School of Medicine, Boston University, University of Washington, Johns Hopkins University, Translational Genomics Research Institute, European Commission, ZonMw, Erasmus Medisch Centrum, Ministero della Salute, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Hjartavernd, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Army Research Office
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OpenAlex ID: W2171241286